Description: (Applicant's Description) The overall objective of the Molecular Therapeutics and Drug Discovery (MT/DD) Program is to promote the development of both basic and clinical research into innovative approaches to drug treatment of solid tumors and hematologic malignancies. The Program is composed of a multidisciplinary group of scientists committed to making basic laboratory observations and translating them into the clinical setting. Both basic and clinical scientists in the Program interact extensively with each other and with faculty in other UPCI programs. The focus of the MT/DD program is to develop mechanistic studies on novel anticancer agents, to identify and characterize new targets, to examine the efficacy of innovative drugs and drug delivery systems, to investigate the mechanisms of drug resistance and to translate these efforts into phase I and phase II clinical trials. Central to the Program's mission is the obtaining of sufficient laboratory-derived data to develop more efficacious clinical therapies against solid human tumors and hematologic malignancies. Specific molecular target areas include transmembrane proteins, tyrosine kinase receptors, hormones and hormone receptors, nuclear structure/matrix, redox and phosphorylation pathways, apoptotic signaling and cell cycle checkpoints. The MT/DD Program also targets drug delivery/tumor vasculature, drug metabolism and pharmacokinetics/ pharmacodynamics as key areas related to both pre-clinical and clinical drug discovery and development. Critical to the goals of this program are the interactions with other basic science areas and clinical programs that result in translation of important and applicable laboratory studies to the clinical setting. The MT/DD Program has focused on establishing a strong basic science foundation for the development of small molecule anti-cancer agents and novel therapeutic approaches to malignancy. Each Program member has a clear commitment to cancer or cancer-related experimental therapeutic design. In addition to basic science development and mechanistic studies, the MT/DD program also has a number of investigators who provide the pre-clinical interface for the development of clinical studies in the Phase I setting.